In vitro biological evaluation and in silico studies of linear diarylheptanoids from Curcuma aromatica Salisb. as urease inhibitors.

Plants of the Zingiberaceae family, specifically those belonging to the Curcuma species, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromatica Salisb. (or so-called "Nghe trang" in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1-3) and six known 3,5-dihydroxyl diarylheptanoids (4-9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4 and 9 significantly inhibit urease, with an IC50 value of 9.6 and 21.4 µM, respectively, more substantial than the positive control, hydroxyurea (IC50 = 77.4 µM). The structure-activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds via our constructed in silico model, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.

A New abeo-Icetexane-Type Diterpenoid from the Stem Barks of Taxus wallichiana.

From a CH2 Cl2 -soluble fraction of the stem barks of Taxus wallichiana, one new abeo-icetexane-type diterpenoid, taxamairin I (1), was isolated. Its absolute configuration was elucidated based on spectroscopic interpretation and time-dependent density functional theory (TD-DFT) calculation of optical rotation. In addition, the plausible biosynthesis pathway for the formation of the new abeo-icetexane-type diterpenoid was proposed. Taxamairin I (1), at a concentration of 100 µM, did not show cytotoxicity against Hep3B human liver cancer cell lines.

Paratrimerin Z, an undescribed chromene derivative from the roots of Paramignya trimera.

From an EtOAc-soluble fraction of the roots of Paramignya trimera, one undescribed chromene derivative, paratrimerin Z (1), was isolated. Its structure was elucidated on the basis of NMR spectroscopic interpretation. The absolute configuration of 1 was determined by the specific rotation analysis of its acid-catalyzed hydrolysis product. Paratrimerin Z (1), at a concentration of 100 µM, did not show cytotoxicity against Hep3B human liver cancer cell line.

A new diphenylheptanoid from the rhizomes of Curcuma zedoaria.

A phytochemical investigation of the rhizomes of Curcuma zedoaria was carried out, leading to the isolation of a new diphenylheptanoid, zedoaroxane A (1), together with four known compounds (2-5). Their structures were elucidated based on NMR spectroscopic data. All isolated compounds possessed α-glucosidase inhibitory activity, with the IC50 values ranging from 35.2 to 89.0 µM, more potent than that of the positive control acarbose (IC50, 214.5 µM).

δ-Tocopherol derivatives from the leaves of Muntingia calabura L.

From an ethyl acetate-soluble fraction of the leaves of Muntingia calabura, one new trimeric δ-tocopherol derivative named as tocomuntin A (1), together with three known δ-tocopherol derivatives (2-4) were isolated. Their structures were elucidated based on the interpretation of NMR and MS spectroscopic data. In this work, δ-tocopherol (3) was found to have α-glucosidase inhibitory activity for the first time (IC50, 47.3 µM).

Paratrimerin I, cytotoxic acridone alkaloid from the roots of Paramignya trimera.

Bioactivity-guided fractionation of the CHCl3-soluble extract of the roots of Paramignya trimera was carried out to obtain a new acridone alkaloid, paratrimerin I. Its structure was elucidated based on NMR spectroscopic data interpretation. Paratrimerin I showed noteworthy cytotoxicity against the HepG2 human hepatocellular and MCF-7 human breast carcinoma cell lines, with the submicromolar IC50 values of 0.43 and 0.26 µM, respectively. The N-methyl, C-4 methoxy, and C-5 hydroxy groups in the acridone skeleton can be proposed as a structural feature for good cytotoxicity.

A new phenolic acid from the wood of Mangifera gedebe.

From the methanol extract of the wood of Mangifera gedebe (Anacardiaceae), we had isolated a new secondary metabolite named gedebic acid (1) and six known compounds (2-7). Their chemical structures were determined by spectroscopic methods as well as comparing with data in the literature. All compounds were tested for α-glucosidase inhibitory activity. Compounds 4-7 showed more potent inhibitory activity, with IC50 values ranging from 45.3 to 142.6 µM, than that of a positive control acarbose (IC50, 214.5 µM).

A new phenylheptanoid from the leaves of Gnetum gnemon L.

Phytochemical study on the EtOAC-soluble extract of the leaves of Gnetum gnemon furnished the isolation of a new phenylheptanoid, gnetumal (1), along with five known compounds (2-6). Their isolation was carried out by using the column chromatography and their structures were elucidated based on the basis of the spectral interpretation. Bioactivity assay of these compounds indicated that gnetumal (1) and p-coumaric acid (5) possessed more potent tyrosinase inhibitory activity, with IC50 values of 31.6 and 2.3 µM, respectively, than that of a positive control kojic acid (IC50; 44.6 µM).

Decumbic anhydride from the stem barks of Swintonia floribunda (Anacardiaceae).

From an EtOAc-soluble fraction of the stem barks of Swintonia floribunda (Anacardiaceae), decumbic anhydride (1) and four known compounds 2-5 were isolated. Their chemical structures were elucidated based on the spectroscopic data interpretation. The GIAO-DFT calculation of 13C NMR chemical shifts was carried out to clarify the structure of 1. The absolute configuration of 1 was assigned based on the Cotton effects in its ECD spectrum. Compound 1 showed potent tyrosinase inhibitory activity with an IC50 value of 52.2 µM.

Tyrosinase inhibitory activity of flavonoids from Artocarpus heterophyllous.

BACKGROUND: Tyrosinase is an oxidoreductase that is very important in medicine and cosmetics because the excessive production of melanin causes hyperpigmentation. The development of novel, effective tyrosinase inhibitors has long been pursued. In preliminary tests, we found that an extract of the wood of Artocarpus heterophyllous (AH) potently inhibited tyrosinase activity. RESULTS: Two new flavonoids, artocaepin E (1) and artocaepin F (2), were isolated from the wood of AH, together with norartocarpetin (3), artocarpanone (4), liquiritigenin (5), steppogenin (6), and dihydromorin (7). Their structures were elucidated using one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry. The absolute configuration of 2 was determined from the circular dichroism (CD) spectrum. Artocarpanone (4) had the most potent tyrosinase inhibitory effect, with an IC50 of 2.0 ± 0.1 µM, followed by artocaepin E (1) and steppogenin (6), with IC50 values of 6.7 ± 0.8 and 7.5 ± 0.5 µM, respectively. A kinetic investigation indicated that 1 showed competitive inhibition, with an inhibition constant (K i) of 6.23 µM. CONCLUSIONS: These results demonstrate that extracts of the wood of AH and its phytochemical constituents are potential sources for skin-whitening agents.Graphical abstractArtocarmin E (1) and artocarmin F (2) were isolated from the wood of Artocarpus heterophyllous. Their structures were elucidated using nuclear magnetic resonance analysis and mass spectrometric methods.